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Spatial heterogeneity of cell-matrix adhesive forces predicts human glioblastoma migration.

Accepted version
Peer-reviewed

Type

Article

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Authors

Rezk, Rasha 
Jia, Bill Zong 
Wendler, Astrid 
Dimov, Ivan 
Watts, Colin 

Abstract

BACKGROUND: Glioblastoma (GBM) is a highly aggressive incurable brain tumor. The main cause of mortality in GBM patients is the invasive rim of cells migrating away from the main tumor mass and invading healthy parts of the brain. Although the motion is driven by forces, our current understanding of the physical factors involved in glioma infiltration remains limited. This study aims to investigate the adhesion properties within and between patients' tumors on a cellular level and test whether these properties correlate with cell migration. METHODS: Six tissue samples were taken from spatially separated sections during 5-aminolevulinic acid (5-ALA) fluorescence-guided surgery. Navigated biopsy samples were collected from strongly fluorescent tumor cores, a weak fluorescent tumor rim, and nonfluorescent tumor margins. A microfluidics device was built to induce controlled shear forces to detach cells from monolayer cultures. Cells were cultured on low modulus polydimethylsiloxane representative of the stiffness of brain tissue. Cell migration and morphology were then obtained using time-lapse microscopy. RESULTS: GBM cell populations from different tumor fractions of the same patient exhibited different migratory and adhesive behaviors. These differences were associated with sampling location and amount of 5-ALA fluorescence. Cells derived from weak- and nonfluorescent tumor tissue were smaller, adhered less well, and migrated quicker than cells derived from strongly fluorescent tumor mass. CONCLUSIONS: GBM tumors are biomechanically heterogeneous. Selecting multiple populations and broad location sampling are therefore important to consider for drug testing.

Description

Keywords

cell migration, cell-matrix adhesion, glioblastoma

Journal Title

Neurooncol Adv

Conference Name

Journal ISSN

2632-2498
2632-2498

Volume Title

2

Publisher

Oxford University Press (OUP)

Rights

All rights reserved
Sponsorship
El Moawad Family (via Nabaa el Mahaba) (Unknown)
European Research Council (240446)
Engineering and Physical Sciences Research Council (EP/L015978/1)
European Research Council (772426)
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